Biotech investors need to keep their heads on a swivel because competition can come from every direction imaginable.
Alnylam Pharmaceuticals (NASDAQ:ALNY) and Ionis Pharmaceuticals (NASDAQ:IONS) looked to be in a two-horse race to develop TTR amyloidosis (ATTR) drugs. Alnylam recently got its drug Onpattro approved, while Ionis Pharmaceuticals and its marketing partner Akcea Therapeutics (NASDAQ:AKCA) should hear about Tegsedi by Oct. 6. Tegsedi was approved in the EU last month.
But the two companies got a surprise in March when Pfizer (NYSE:PFE) said a clinical trial for its competing drug tafamidis was successful. The drug was approved in the EU under the brand name Vyndaqel in 2011 but hadn't gotten much traction with the previous limited efficacy data -- in fact, the Food and Drug Administration rejected the drug based on the same data. Pfizer is scheduled to present the details of the clinical trial results at the European Society of Cardiology (ESC) Congress and review the data with investors on Monday.
Investors also have to watch Eidos Therapeutics (NASDAQ:EIDX), which has a mid-stage ATTR drug in development. Top-line results from the phase 2 trial are expected before the end of the year. Investors would be excused for not knowing about Eidos Therapeutics, since it was a private company until its late-June IPO.
That pesky TTR protein
ATTR is caused by the aggregation of the transthyretin (TTR) protein, mainly in the heart and nervous system. Mutations in the TTR protein, which carries thyroid hormone and vitamin A through the bloodstream, cause it to fold improperly, which leads to the aggregation. The protein can also build up in patients with normal "wild type" protein, especially in older individuals.
Alnylam's Onpattro and Ionis' Tegsedi work by knocking down the TTR protein levels. Onpattro does it though a process of RNA interference, while Tegsedi works through RNA antisense, but the end result is the same: A decrease in the RNA that's used to make the TTR protein results in smaller amounts of the protein. Both drugs have shown solid efficacy on neurological symptoms, and Alnylam has some data showing its drug helps heart complications as well.
Pfizer's tafamidis and Eidos Therapeutics' AG10, on the other hand, work by stabilizing the TTR protein, reducing the chance that it aggregates in the heart and nervous system. Pfizer has had some trouble showing the strategy works for neurology symptoms, but the top-line results released in April suggest stabilizing TTR can help patients with heart symptoms -- although we'll have to wait for the ESC presentation to find out exactly how much it's helping.
Without seeing head-to-head data, it's hard to know whether knocking down TTR levels or stabilizing the protein will result in better relief of symptoms. You could imagine that knocking down the protein might result in quicker removal of the aggregated protein, but that has to be balanced by the loss of the normal function of the TTR protein.
Tafamidis and AG10 are both oral medications, a form patients would prefer over Onpattro and Tegsedi, which have to be injected or infused. Of course, given the fatality of ATTR, efficacy should end up playing a bigger role in sales than the convenience factor.
Importantly, this may not be a winner-take-all market. Onpattro and Tegsedi don't knock down all the TTR protein, so adding tafamidis or AG10 might further decrease ATTR symptoms by stabilizing the remaining protein.
Alnylam clearly has the advantage as it is first out of the gate in the U.S., but it's still too early to call a winner before data from Pfizer and Eidos comes in. And adding to the competition, Alnylam and Ionis Pharmaceuticals are both developing follow-on compounds that can be dosed less frequently, which will further complicate the landscape in the coming years.
All told, it's going to be an interesting competition in the ATTR space.